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Status epilepticus is a life-threatening neurological emergency that affects both adults and children. Approximately 36% of episodes of status epilepticus do not respond to the current preferred first-line treatment, benzodiazepines. The proportion of episodes that are refractory to benzodiazepines is higher in low-income and middle-income countries (LMICs) than in high-income countries (HICs). Evidence suggests that longer episodes of status epilepticus alter brain physiology, thereby contributing to the emergence of benzodiazepine resistance. Such changes include alterations in GABAA receptor function and in the transmembrane gradient for chloride, both of which erode the ability of benzodiazepines to enhance inhibitory synaptic signalling. Often, current management guidelines for status epilepticus do not account for these duration-related changes in pathophysiology, which might differentially impact individuals in LMICs, where the average time taken to reach medical attention is longer than in HICs. In this Perspective article, we aim to combine clinical insights and the latest evidence from basic science to inspire a new, context-specific approach to efficiently managing status epilepticus. [ABSTRACT FROM AUTHOR]

Network control theory provides a framework by which neurophysiological dynamics of the brain can be modelled as a function of the structural connectome constructed from diffusion MRI. Average controllability describes the ability of a region to drive the brain to easy-to-reach neurophysiological states whilst modal controllability describes the ability of a region to drive the brain to difficult-to-reach states. In this study, we identify increases in mean average and modal controllability in children with drug-resistant epilepsy compared to healthy controls. Using simulations, we purport that these changes may be a result of increased thalamocortical connectivity. At the node level, we demonstrate decreased modal controllability in the thalamus and posterior cingulate regions. In those undergoing resective surgery, we also demonstrate increased modal controllability of the resected parcels, a finding specific to patients who were rendered seizure free following surgery. Changes in controllability are a manifestation of brain network dysfunction in epilepsy and may be a useful construct to understand the pathophysiology of this archetypical network disease. Understanding the mechanisms underlying these controllability changes may also facilitate the design of network-focussed interventions that seek to normalise network structure and function. Children with drug-resistant epilepsy exhibit distinct structural connectomes and changes in network controllability from healthy controls, providing further insight into the pathophysiology of this disease. [ABSTRACT FROM AUTHOR]

Seizures are a prominent feature in N-Methyl-D-Aspartate receptor antibody (NMDAR antibody) encephalitis, a distinct neuro-immunological disorder in which specific human autoantibodies bind and crosslink the surface of NMDAR proteins thereby causing internalization and a state of NMDAR hypofunction. To further understand ictogenesis in this disorder, and to test a potential treatment compound, we developed an NMDAR antibody mediated rat seizure model that displays spontaneous epileptiform activity in vivo and in vitro. Using a combination of electrophysiological and dynamic causal modelling techniques we show that, contrary to expectation, reduction of synaptic excitatory, but not inhibitory, neurotransmission underlies the ictal events through alterations in the dynamical behaviour of microcircuits in brain tissue. Moreover, in vitro application of a neurosteroid, pregnenolone sulphate, that upregulates NMDARs, reduced established ictal activity. This proof-of-concept study highlights the complexity of circuit disturbances that may lead to seizures and the potential use of receptor-specific treatments in antibody-mediated seizures and epilepsy. Sukhvir Wright et al. present a NMDAR antibody-induced model of encephalitis in rats and use in vitro, in vivo, and in silico electrophysiology to examine alterations in neural circuit behavior. Their results suggest that reduction of NMDARs leads to increased excitability and seizure activity, and highlights the potential use of receptor-specific treatments in antibody-mediated seizures and epilepsy. [ABSTRACT FROM AUTHOR]

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Neurological disorders such as epilepsy arise from disrupted brain networks. Our capacity to treat these disorders is limited by our inability to map these networks at sufficient temporal and spatial scales to target interventions. Current best techniques either sample broad areas at low temporal resolution (e.g. calcium imaging) or record from discrete regions at high temporal resolution (e.g. electrophysiology). This limitation hampers our ability to understand and intervene in aberrations of network dynamics. Here we present a technique to map the onset and spatiotemporal spread of acute epileptic seizures in vivo by simultaneously recording high bandwidth microelectrocorticography and calcium fluorescence using transparent graphene microelectrode arrays. We integrate dynamic data features from both modalities using non-negative matrix factorization to identify sequential spatiotemporal patterns of seizure onset and evolution, revealing how the temporal progression of ictal electrophysiology is linked to the spatial evolution of the recruited seizure core. This integrated analysis of multimodal data reveals otherwise hidden state transitions in the spatial and temporal progression of acute seizures. The techniques demonstrated here may enable future targeted therapeutic interventions and novel spatially embedded models of local circuit dynamics during seizure onset and evolution. Driscoll, Rosch et al. design transparent graphene-based surface probes to achieve simultaneous electrophysiological recording and calcium imaging of epileptic seizures in mice. This method could be used to investigate circuit dynamics during seizure onset and evolution with high temporal and spatial resolution. [ABSTRACT FROM AUTHOR]

Reference 271 should have read "Kharod, S. C., Carter, B. M. & Kadam, S. D. Pharmaco-resistant neonatal seizures: critical mechanistic insights from a chemoconvulsant model. These errors have now been corrected in the HTML and PDF versions of the article. At the end of the sentence "This more nuanced understanding of GABAergic signalling in the neonatal brain, particularly regarding the potential role of neuronal NKCC1, has inspired further exploration into how manipulating this co-transporter might affect neonatal seizures and potentially rescue anti-seizure effects of GABA SB A sb R modulators", the following reference should also have been cited "Kang, S. K., Markowitz, G. H., Kim, S. T., Johnston, M. V. & Kadam, S. D. Age-and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters. [Extracted from the article]